Pneumonia is an ailment that can be lethal, particularly to the elderly and young. Every year, approximately 1.3 million children under the age of five die from pneumonia, mostly in the developing world. Infection by the bacterium, Streptococcus pneumoniae (also referred herein as “pneumococcus”), the most common cause of severe pneumonia, kills more than half a million children annually. While even healthy adults may be infected by S. pneumoniae, the elderly, immunocompromised individuals, and children are at greatest risk from the disease. Pneumococcus can also cause bacterial sepsis, bacterial sinusitis, and bacterial meningitis, and is the leading cause of middle ear infection (otitis media).
S. pneumoniae strains vary by region, and there are more than 94 capsular serotypes. While there has been some success in making pneumococcal vaccines, current pneumococcal vaccines do not protect against most pneumococcal capsular serotypes. For example, one currently marketed vaccine, PREVNAR-13® (Wyeth LLC, marketed by Pfizer, New York, N.Y.), is only partially efficacious, protecting against only 13 of the 94 or so pneumococcal capsular serotypes. Another marketed vaccine, PNEUMOVAX®-23 (Merck, Kenilworth, N.J.), offers no protection for children less than two years old, and no protection for older children and adults against 71 of the 94 or so pneumococcal capsular serotypes.
Accordingly, there has been an acute desire to find a “common protein” or “universal” vaccine that would be useful for immunizing against all or nearly all pneumococcal strains (currently ˜94 known), a supermajority, e.g., at least 80%, or at least a majority, e.g., greater than 50%, of the known pneumococcal strains. A critical barrier to the development of such a “common protein” vaccine has been pneumococcal antigenic diversity driven by host immunological selective pressure. The paradigm for development of a common protein vaccine has primarily been empirical, top-down, trial and error testing of known antigenic outer surface protein candidates. Such an approach has yielded poor results primarily because promiscuously recombinant bacteria like S. pneumoniae are adept at “immune escape”, based on the fact that the immunologically active regions of nearly all major surface proteins that have been examined mutate constantly. Copies of a mutated gene that provides an S. pneumoniae cell with a selective advantage for evading attack by an immune response will be rapidly transferred from the mutant cell to recipient cells owing to a promiscuous horizontal (lateral) gene transfer system with subsequent recombination of the mutated gene (recombinational mutation) into the genomes of the recipient cells.
Clearly, needs remain for compositions and methods for identifying, treating, or preventing infections by S. pneumoniae that are more resistant to the adaptive ability of S. pneumoniae cells to evade an immune response.